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The sepsis syndrome . Divya Ahuja, M.D. November , 2009. Severe Sepsis is a Significant Healthcare Burden . Sepsis consumes significant healthcare resources. In a study of patients who develop sepsis and survive: ICU stay prolonged an additional 8 days.

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the sepsis syndrome

The sepsis syndrome

Divya Ahuja, M.D.

November , 2009

severe sepsis is a significant healthcare burden
Severe Sepsis is a Significant Healthcare Burden
  • Sepsis consumes significant healthcare resources.
  • In a study of patients who develop sepsis and survive:
    • ICU stay prolonged an additional 8 days.
    • Additional costs incurred were $40,890/ patient.
  • Estimated annual healthcare costs due to severe sepsis in U.S. exceed $16 billion.
  • In the US, more than 500 patients die of severe sepsis daily.
revised definitions
Revised definitions
  • Systemic inflammatory response syndrome (SIRS)
  • Sepsis
  • Severe sepsis
  • Septic shock
systemic inflammatory response syndrome sirs
Systemic Inflammatory Response Syndrome (SIRS)
  • Two or more of the following
    • temperature > 38 degrees C (100.4 F)
    • respirations > 20/minute
    • Heart rate > 90 beats per minute
    • leukocyte count > 12,000/cmm or < 4000/cmm or with > 10% band forms
definitions accp sccm
Definitions (ACCP/SCCM)
  • Sepsis:
    • Known or suspected infection, plus
    • >2 SIRS Criteria.
  • Severe Sepsis:
    • Sepsis plus >1 organ dysfunction.
    • Multi Organ Dysfunction Syndrome.
    • Septic Shock.
relationship between sepsis and sirs
Relationship Between Sepsis and SIRS









some etiologies of sepsis
Some etiologies of sepsis
  • Pneumonia
  • Bacteremia/endocarditis
  • Skin and soft tissue infection
  • Meningitis
  • Urosepsis
  • Intrabdominal infection secondary to viscus rupture
  • Pelvic inflammatory disease
  • Etc., etc., etc.
septic shock
Septic shock
  • Definition: Sepsis-induced hypotension despite fluid resuscitation and/or inotropic support, plus hypoperfusion abnormalities
  • The hallmark of septic shock is low systemic vascular resistance, which distinguishes it from hemorrhagic shock and cardiogenic shock.
clinical signs of septic shock
Clinical Signs of Septic Shock
  • Myocardial Depression.
  • Altered Vasculature.
  • Altered Organ Perfusion.
  • Imbalance of O2 delivery and Consumption.
  • Metabolic (Lactic) Acidosis.
definitions accp sccm12
Definitions (ACCP/SCCM):
  • Multiple Organ Dysfunction Syndrome (MODS): The presence of altered organ function in an acutely ill patient such that homeostasis cannot be maintained without intervention.
multiple organ failure
Multiple Organ Failure
  • Some physiologic descriptors
    • Serum creatinine
    • Platelet count
    • pO2/FiO2 ratio
    • Serum bilirubin
    • Glasgow coma score








Microvascular Plugging



Maldistribution of Microvascular Blood Flow


Cell Death

Organ Dysfunction

case 1
Case #1
  • 20-year-old college student
  • General malaise, low-grade fever, and rapid development of purplish discoloration on his face. (from when he left his house to the time he arrived at the emergency room).
  • Blood cultures were drawn and he was admitted to the intensive care unit
  • Febrile, tachycardic, systolic BP-70
  • Creatinine- 3.6, poor urine output
  • Platelets-46000
  • INR- 2.6
  • Obtunded mental status
  • Needing maximum ventilatory support
case 1 continued
Case # 1 continued
  • Meningococcemia with Waterhouse-Friderichsen Syndrome and DIC
  • Treat with penicillin, ceftriaxone or chloramphenicol.
  • Family members and hospital employees in contact with respiratory secretions should receive prophylaxis.
continuum of severity
Continuum of severity
  • Incidence of positive blood cultures increases along the continuum
  • Increased mortality rate
  • Severe organ dysfunction manifested as
    • Acute respiratory distress syndrome
    • Acute renal failure
    • Disseminated intravascular coagulation
evaluation of blood cultures
Evaluation of blood cultures
  • True-positive versus false-positive (contamination; pseudobacteremia)
  • Transient versus intermittent versus continuous
  • Polymicrobial versus unimicrobial
  • Primary versus secondary
clues to contamination
Clues to contamination
  • Microorganisms that are usually not pathogenic, unless isolated from multiple cultures (e.g., coagulase-negative staphylococci; Bacillus species, corynebacterium)
  • < 2 positive cultures and/or delayed growth and/or < 1 cfu/ml
  • Doesn’t “fit” the clinical picture
  • Repeat blood cultures are helpful in differentiating between contamination and true bacteremia
patterns of bacteremia
Patterns of bacteremia
  • Transient: caused by manipulation of a flora-containing body surface
  • Intermittent: typical of most infections giving rise to positive blood cultures
  • Sustained (or continuous): characteristic of intravascular infections--endocarditis, endarteritis, suppurative thrombophlebitis, infected AV fistula
bacteremia and sepsis
Bacteremia and sepsis
  • Persistent bacteremia is a poor prognostic marker
  • Staphylococcus aureus bacteremia is a common ID consult and has a 10-30% incidence of endocarditis associated with it
  • Severe sepsis: Blood cultures are positive in 20% to 40% of cases
  • Septic shock: Blood cultures are positive in 40% to 70% of cases
risk factors for nosocomial sepsis
Risk factors for nosocomial sepsis
  • Gram-negative bacilli: diabetes mellitus; tumors; cirrhosis; burns; invasive procedures; neutropenia
  • Gram-positive cocci: vascular access lines, devices
  • Fungi: immunosuppression; broad-spectrum antibiotic therapy
clinical findings in sepsis
Clinical findings in sepsis
  • Early: apprehension, hyperventilation, altered mental status
  • Complications: hypotension, bleeding, leukopenia, thrombocytopenia, organ failure
  • Lungs: cyanosis, acidosis, full-blown ARDS
clinical findings in sepsis 2
Clinical findings in sepsis (2)
  • Kidneys: oliguria, anuria, tubular necrosis
  • Liver: jaundice and transaminitis
  • Heart: heart failure, stunned myocardium
  • Gastrointestinal: nausea, vomiting, diarrhea, stress ulceration
  • Systemic: lactic acidosis
clinical findings in sepsis 3
Clinical findings in sepsis (3)
  • Petechiae early in course: suspect especially meningococcemia, RMSF
  • Ecthyma gangrenosum: Ps. aeruginosa
  • Generalized erythroderma: Toxic Shock Syndrome
skin lesions in septicemias 1
Skin lesions in septicemias (1)
  • Neisseria meningitidis: erythematous macules or petechiae and purpura
  • Rocky Mountain spotted fever: petechiae, purpura
  • Staphylococcus aureus: “purulent purpura”
  • Pseudomonas aeruginosa: ecthyma gangrenosum
skin lesions in septicemia 2
Skin lesions in septicemia (2)
  • Salmonella typhi: “Rose spots”
  • Hemophilus influenzae: cellulitis
  • Endocarditis: petechiae; Osler’s nodes (painful lesions of finger and toe pads); Janeway lesions (painless lesions of palms or soles)
  • Anthrax: papules-->vesicles-->eschar
  • Fungemias

A 50 yo man presents to emergency room with severe pain and swelling of LLE. On exam, temperature is 40.0 ºC, pulse rate is 135/min, respiration rate is 35/min, and blood pressure is 80/40

which of the following is the most appropriate initial therapy
Which of the following is the most appropriate initial therapy?
  • LLE elevation
  • X-ray of LLE
  • Surgical consultation
  • Oral antibiotics
necrotizing fasciitis
Necrotizing fasciitis
  • Necrotizing fasciitis usually results from an initial break in skin (trauma or surgery)
  • It is deep: may involve the fascial and/or muscle compartments
  • The initial presentation is that of cellulitis
necrotizing fasciitis red flags
Necrotizing fasciitis: Red flags
  • Severe pain (out of proportion of skin findings)
  • Bullae (due to occlusion of deep blood vessels)
  • Skin necrosis or ecchymosis
  • Gas in soft tissue (palpation or imaging)
  • Systemic toxicity
  • Rapid spread during antibiotic therapy
necrotizing fasciitis40
Necrotizing fasciitis
  • Monomicrobial: S. pyogenes, S. aureus, anaerobic streptococci,…. Most are community acquired and present in the limbs in patients with DM or vascular insufficiency
  • Polymicrobial: aerobic and anaerobic (bowel flora), Usually associated with abdominal surgical procedures, decubitus ulcer, perianal ulcer, bartholin abscess, IV drug injection
staphylococcal bacteremia
Staphylococcal bacteremia
  • Complications: endocarditis; metastatic infection; sepsis syndrome
  • Staphylococci adhere avidly to endothelial cells and bind through adhesin-receptor interactions
  • Fulminant onset; high fever, erythematous rash with subsequent desquamation, and multiorgan damage
  • DDx: Rocky Mountain spotted fever, streptococcal scarlet fever, leptospirosis
streptococcal toxic shock syndrome
Streptococcal toxic shock syndrome
  • Early onset of shock and organ failure associated with isolation of group A streptococci
  • Necrotizing fasciitis present in about 50% of cases
  • Early symptoms: Myalgias, malaise, chills, fever, nausea, vomiting, diarrhea
  • Pain at minor trauma site may be first symptom
sepsis in the asplenic patient
Sepsis in the asplenic patient
  • Frequently fulminant with massive bacteremia
  • Streptococcus pneumoniae accounts for 50% to 90% of infections and 60% of deaths
  • Other pathogens: Haemophilus influenzae, Neisseria meningitidis, Capnocytophagacanimorsus (after dog bites), Babesia microti (babesiosis)
64 year old wm
64 year old WM
  • Presents with fever, hypotension, cellulitis with bullous skin lesions
  • PMH: cirrhosis
  • SH: recently returned from New Orleans, likes oysters
vibrio vulnificus sepsis
Vibrio vulnificussepsis
  • Organism found in warm seawater and in shellfish (90% of deaths due to seafood in U.S.)
  • Cirrhosis a major risk factor to sepsis, with rapid onset
  • Chills, fever, characteristic skin lesions (bullae with hemorrhagic fluid; necrotizing fasciitis, other)
  • Also causes wound infection after exposure to salt water
41 year old wm
41 year old WM
  • Fever, “worst headache ever,” myalgias, rash
  • Returned from family camping trip in Smoky Mountain National Park 1 week PTA
rocky mountain spotted fever
Rocky Mountain spotted fever
  • Generalized infection of vascular endothelium
  • Headache typically severe. Fever may be low-grade and rash may be absent (“spotless fever”) when patient first seen
  • Suspect with flu-like illness and severe headache in endemic areas!
65 year old woman
65 year old woman
  • PMH diabetes
  • During influenza epidemic, presents with fever, chills, aching all over (myalgia)
  • PE: bibasilar rales; no murmur, febrile
  • Blood cultures (2/2) are positive for S. aureus
infective endocarditis definitions
Infective endocarditis: definitions
  • Septic vegetations of the endocardium usually involving the heart valves or other areas of turbulent flow
  • Acute endocarditis occurs on normal heart valves, is caused by highly virulent bacteria and leads to death in < 6 weeks
  • Subacute endocarditis is caused by less virulent bacteria and has a more indolent course.
diagnosis of endocarditis
Diagnosis of endocarditis
  • Revised Duke Criteria : positive blood cultures plus echocardiography with or without minor criteria
  • Heart murmurs (especially regurgitant)
  • Splinter hemorrhages (nail beds)
  • Osler nodes (finger pulps; painful)
  • Petechiae; “pustular purpura” (Staph)
  • Roth spots (fundi)
etiologies of endocarditis
Etiologies of endocarditis
  • Viridans streptococci most common (30-40%) Staphylococci - 20-30%
  • Other streptococci include enterococci and Streptococcus bovis
  • Less common: aerobic gram-negative rods; HACEK organisms; fungi; anaerobic bacteria; Brucella; Coxiella burnetti; Chlamydia psittaci
  • “Culture-negative” (<5% to 24%)
therapeutic strategies in sepsis
Therapeutic Strategies in Sepsis
  • Optimize Organ Perfusion
    • Expand effective blood volume.
    • Hemodynamic monitoring.
    • Early goal-directed therapy.
    • Pressors may be necessary
therapeutic strategies in sepsis59
Therapeutic Strategies in Sepsis
  • Control Infection Source
    • Drainage
      • Surgical
      • Radiologically-guided
    • Culture-directed antimicrobial therapy
    • Support of reticuloendothelial system
      • Enteral / parenteral nutritional support
      • Minimize immunosuppressive therapies
therapeutic strategies in sepsis60
Therapeutic Strategies in Sepsis
  • Support Dysfunctional Organ Systems
    • Renal replacement therapies (CVVHD, HD).
    • Cardiovascular support (pressors, inotropes).
    • Mechanical ventilation.
    • Transfusion for hematologic dysfunction.
    • Minimize exposure to hepatotoxic and nephrotoxic therapies.
sepsis summary
  • Look at the host (age, immunedeficiency,-HIV, cancer, steroids, cirrhosis, dialysis,
  • Clinical assessment for MOD (vitals, perfusion, mental status, urine output)
  • Lab parameters-platelets, creatinine, coags, leukocytosis vs. leukopenia
  • Hemodyanamic, ventilatory support, antibiotics
  • HIT HARD and HIT EARLY and then deescalate based on emerging microbiological data